July 28, 2013 A new blood test can be used to discriminate between people with Alzheimer's disease and healthy controls. It's hoped the test, described in the open access journal Genome Biology, could one day be used to help diagnose the disease and other degenerative disorders.
Alzheimer's disease, the most common form of dementia, can only be diagnosed with certainty at autopsy, so the hunt is on to find reliable, non-invasive biomarkers for diagnosis in the living. Andreas Keller and colleagues focused on microRNAs (miRNAs), small non-coding RNA molecules known to influence the way genes are expressed, and which can be found circulating in bodily fluids including blood.
The team, from Saarland University and Siemens Healthcare highlighted and tested a panel of 12 miRNAs, levels of which were found to be different amongst a small sample of Alzheimer's patients and healthy controls. In a much bigger sample, the test reliably distinguished between the two groups.
Decent biomarkers need to be accurate, sensitive (able to correctly identify people with the disease) and specific (able to correctly pinpoint people without the disease). The new test scores over 90% on all three measures. But whilst the test shows obvious promise, it still needs to be validated for clinical use, and may eventually work best when combined with other standard diagnostic tools, such as imaging, the authors say.
As people with other brain disorders can sometimes show Alzheimer's-like symptoms, the team also looked for the miRNA signature in other patient groups. The test distinguished controls from people with various psychological disorders, such as schizophrenia and depression, with over 95% accuracy, and from patients with other neurodegenerative disorders, such as mild cognitive impairment and Parkinson's disease, with lower accuracy. It also discriminated between Alzheimer's patients and patients with other neurodegenerative disorders, with an accuracy of around 75%. But by tweaking the miRNAs used in the test, accuracy could be improved.
The work builds on previous studies highlighting the potential of miRNAs as blood-based biomarkers for many diseases, including numerous cancers, and suggests that miRNAs could yield useful biomarkers for various brain disorders. But it also sheds light on the mechanisms underpinning Alzheimer's disease. Two of the miRNAs are known involved in amyloid precursor protein processing, which itself is involved in the formation of plaques, a classic hallmark of Alzheimer's disease. And many of the miRNAs are believed to influence the growth and shape of neurons in the developing brain.
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- Petra Leidinger, Christina Backes, Stephanie Deutscher, Katja Schmitt, Sabine C Muller, Karen Frese, Jan Haas, Klemens Ruprecht, Friedemann Paul, Cord Stahler, Christoph JG Lang, Benjamin Meder, Tamas Bartfai, Eckart Meese, Andreas Keller. A blood based 12-miRNA signature of Alzheimer disease patients. Genome Biology, 2013; 14 (7): R78 DOI: 10.1186/gb-2013-14-7-r78
- Thalyana Smith-Vikos, Frank J Slack. MicroRNAs circulate around Alzheimer's disease. Genome Biology, 2013; 14 (7): 125 DOI: 10.1186/gb-2013-14-7-125
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